1. Field of the Invention
The present invention relates generally to the delivery of medicaments, and more particularly, to devices and methods for delivering therapeutic agents directly to intraocular tissue and for withdrawing materials from within areas of the eye, such as the vitreous humor. These devices and methods are advantageous for many reasons, among which is that insertion of such a device into the eye necessitates forming an insertion site that is small enough to require no sutures to close, i.e., that is self-sealing, following post-treatment removal of the device.
2. Background
The delivery of drugs to the eye, especially the retina, presents many challenges, most of which are owed to the geometry, delicacy and/or behavior of the eye and its components.
For example, it is known in the art that ocular absorption of systemically administered pharmacological agents and medicaments is limited by the blood ocular barrier, i.e., tight junctions of the retinal pigment epithelium and vascular endothelial cells. And although high systemic doses of such medicaments and agents are capable of penetrating this barrier in relatively small amounts, a realistic risk of systemic toxicity accompanies such a course of treatment.
Topical delivery of pharmacological agents and medicaments, although involving fewer risks, has proven to be an equally ineffective treatment method. Not only do the complex hydrophobic/hydrophilic properties of the cornea and sclera hamper absorption of topically delivered agents, but data also indicates that it is not unusual for up to 85% of topically-applied agents to be removed by the eye's blink mechanism/reflex.
Intravitreal injection of a drug is an effective means of delivering the drug to the posterior segment of the eye in high concentrations, but it necessarily requires follow-up injections in order to maintain an adequate therapeutic concentration. This, in turn, presents problems because each additional intraocular injection carries with it a realistic risk of infection, hemorrhage and/or retinal detachment.
Moreover, even if intravitreal injection techniques were not otherwise problematic, such techniques have also proven inadequate for performing cell transplantation and gene therapy, which require, respectively, subretinal placement of cells and subretinal delivery of gene vectors.
Several specific prior art techniques for subretinal delivery of agents are known, e.g., those described in U.S. Pat. Nos. 5,273,530 and 5,409,457. Another such approach is discussed in Investigative Ophthalmology and Visual Science 30:1684 (1989), which details a microspatula device for administering cells to the eye through a trans-scleral or trans-corneal incision. Yet another instrument employed by those in the art is a glass pipette, which is used to replace cells in the retina by being introduced the eye anteriorly through an incision via the scleral route (Investigative Ophthalmology and Visual Science 28:1131(1987)).
Still other systems for subretinal drug injection, and for gene delivery are described in Human Gene Therapy 11:449 (2000) and Investigative Ophthalmology and Visual Science 35:2535 (1994). And yet another instrument known in the art to serve this purpose is a glass micro cannula.
A common feature of these techniques/instruments is that they necessarily require the creation of a surgical incision at the outset of a procedure, and/or the use of sutures following completion of the procedure. This, in turn, increases the duration, cost, and realistic risks of corneal ulceration, cataract formation, intraocular infection, and/or vitreous loss that accompany these procedures.